Ectodermal Influx and Cell Hypertrophy Provide Early Growth for All Murine Mammary Rudiments, and Are Differentially Regulated among Them by Gli3

Lee, May Yin; Racine, Victor; Jagadpramana, Peter; Sun, Li; Yu, Weimiao; Du, Tiehua; Spencer‐Dene, Bradley; Rubin, Nicole; Le, Lendy; Ndiaye, Delphine; Bellusci, Savério; Kratochwil, Klaus; Veltmaat, Jacqueline M.

doi:10.1371/journal.pone.0026242

Cited by 37 publications

(50 citation statements)

References 37 publications

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“…Deletion of Gli3 causes inappropriate encroachment of hair follicles close to MR2, which itself protrudes abnormally from Gli3 mutant ectoderm, similar to cervical mammary placodes in W6cre/CAGC8 mutants. Interestingly, deletion of Gli3 also prevents the normal regression of mammary buds in male mice, comparable to the persistence of male MRs within the anterior ectopic zone of W6cre/CAGC8 mice (Chandramouli et al, 2013;Hatsell and Cowin, 2006;Lee et al, 2011Lee et al, , 2013Ulloa et al, 2007).…”

Section: Ectodermal Tbx3 Ablation Abolishes Both Ectopic and Normal Mmentioning

confidence: 88%

“…Ectopic mammary glands occur most commonly at inappropriate sites along these lines. Evidence in rabbits and mice suggests that mammary placodes form by migration of epithelial cells into and along the mammary lines, resulting in the five pairs of MRs developing non-sequentially at characteristic positions along the body axis (Lee et al, 2011;Propper, 1978). Molecular requirements differ among the pairs of mammary placodes, and differential gene expression profiles may underlie some of the heterogeneous attributes and susceptibilities to tumor incidence in adult mammary glands .…”

Section: Introductionmentioning

confidence: 99%

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HOXC8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression, and Wnt/β-catenin signaling

Carroll

Capecchi

2015

Development

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The role of Hox genes in the formation of cutaneous accessory organs such as hair follicles and mammary glands has proved elusive, a likely consequence of overlapping function and expression among various homeobox factors. Lineage and immunohistochemical analysis of Hoxc8 in mice revealed that this midthoracic Hox gene has transient but strong regional expression in ventrolateral surface ectoderm at E10.5, much earlier than previously reported. Targeted mice were generated to conditionally misexpress Hoxc8 from the Rosa locus using select Cre drivers, which significantly expanded the domain of thoracic identity in mutant embryos. Accompanying this expansion was the induction of paired zones of ectopic mammary development in the cervical region, which generated between three and five pairs of mammary placodes anterior to the first wild-type mammary rudiment. These rudiments expressed the mammary placode markers Wnt10b and Tbx3 and were labeled by antibodies to the mammary mesenchyme markers ERα and androgen receptor. Somitic Fgf10 expression, which is required for normal mammary line formation, was upregulated in mutant cervical somites, and conditional ablation of ectodermal Tbx3 expression eliminated all normally positioned and ectopic mammary placodes. We present evidence that Hoxc8 participates in regulating the initiation stages of mammary placode morphogenesis, and suggest that this and other Hox genes are likely to have important roles during regional specification and initiation of these and other cutaneous accessory organs.

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Section: Ectodermal Tbx3 Ablation Abolishes Both Ectopic and Normal Mmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

HOXC8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression, and Wnt/β-catenin signaling

Carroll

Capecchi

2015

Development

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“…The molecular and cellular basis of this transition is still unclear. However, earlier morphological studies in rabbits and recent cell-tracing experiments in mice suggested that the formation and growth of mammary placodes involve migration and reassembly of the mammary epithelial cells (Propper, 1978;Lee et al, 2011). This dynamic mode of placode formation suggests that mammary glands may have adopted a distinct molecular mechanism for placode induction.…”

Section: Introductionmentioning

confidence: 99%

Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling

et al. 2013

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SUMMARYThe future site of skin appendage development is marked by a placode during embryogenesis. Although Wnt/-catenin signaling is known to be essential for skin appendage development, it is unclear which cellular processes are controlled by the signaling and how the precise level of the signaling activity is achieved during placode formation. We have investigated roles for Lrp4 and its potential ligand Wise (Sostdc1) in mammary and other skin appendage placodes. Lrp4 mutant mice displayed a delay in placode initiation and changes in distribution and number of mammary precursor cells leading to abnormal morphology, number and position of mammary placodes. These Lrp4 mammary defects, as well as limb defects, were associated with elevated Wnt/-catenin signaling and were rescued by reducing the dose of the Wnt co-receptor genes Lrp5 and Lrp6, or by inactivating the gene encoding -catenin. Wise-null mice phenocopied a subset of the Lrp4 mammary defects and Wise overexpression reduced the number of mammary precursor cells. Genetic epistasis analyses suggest that Wise requires Lrp4 to exert its function and that, together, they have a role in limiting mammary fate, but Lrp4 has an early Wise-independent role in facilitating placode formation. Lrp4 and Wise mutants also share defects in vibrissa and hair follicle development, suggesting that the roles played by Lrp4 and Wise are common to skin appendages. Our study presents genetic evidence for interplay between Lrp4 and Wise in inhibiting Wnt/-catenin signaling and provides an insight into how modulation of Wnt/-catenin signaling controls cellular processes important for skin placode formation.

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“…1B). The thickness and shape of the collected mesenchymal cups varied slightly, along with the variation in shape of the five mammary buds and their adjacent mammary mesenchyme (Lee et al, 2011), but was fairly consistent among replicates of the same bud.…”

Section: Rehydration and Precise Dissectionmentioning

confidence: 88%

A non-enzymatic microsurgical dissection technique of mouse embryonic tissues for gene expression profiling applications

Sun¹,

Lee²,

Veltmaat³

2011

Int. J. Dev. Biol.

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With the increased use of gene expression profiling to identify molecular regulators of cellular and developmental mechanisms, developmental biologists face a new challenge in dissecting tissues without cross-contamination or change in RNA profile, and with intact RNA integrity. We have developed a technique that overcomes these problems. We took the dissection of rudimentary mouse embryonic mammary glands as an example, as these structures are particularly difficult to separate from their contiguous ectoderm and strongly adhering mesenchyme. Contrary to conventional enzymatic tissue-separation methods, we blocked transcriptional activity prior to dissection and protected RNA from degradation during dissection, by the use of RNAlater. While RNAlater dehydrates specimens so severely that it interferes with visibility and clean dissection of organs or tissues, we established rehydration conditions that in fact facilitated tissue separation and shortened dissection time to about 10 minutes. The extracted RNA had an excellent quality, rendering it perfectly suitable for transcriptional profiling. Visual inspection of separated tissues and tissue specific gene expression analysis by microarray and RT-PCR confirmed that the tissues were separated with minimal or no cross-contamination. We show that this dissection method can be applied to a broad variety of organs, and that the tissue is still amenable to protein detection. In conclusion, this is a rapid, cheap and effective non-enzymatic tissue separation method which greatly facilitates the exploration of molecular mechanisms in organ formation.

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Ectodermal Influx and Cell Hypertrophy Provide Early Growth for All Murine Mammary Rudiments, and Are Differentially Regulated among Them by Gli3

Cited by 37 publications

References 37 publications

HOXC8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression, and Wnt/β-catenin signaling

HOXC8 initiates an ectopic mammary program by regulating Fgf10 and Tbx3 expression, and Wnt/β-catenin signaling

Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling

A non-enzymatic microsurgical dissection technique of mouse embryonic tissues for gene expression profiling applications

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